Folate Targeting Peptide Conjugates for Inflammatory Response Suppression.

Background and objective: Protein kinases known as mitogen-activated protein kinases (MAPKs) are responsible for regulating a wide variety of physiological cell responses by generating and release of inflammatory mediators. Suppressing these inflammatory mediators can be utilized to control the propagation of inflammation. During the course of this research, we created folate-targeted MK2 inhibitor conjugates and analyzed the antiinflammatory effects of these compounds.

Methods: Using RAW264.7 cells, which are generated from murine macrophages, as an in vitro model. We synthesize and evaluated a folate linked peptide MK2 inhibitor. The cytotoxicity was assessed using the ELISA kits, CCK- 8 test kit, NO concentration and inflammatory factors TNF-, IL-1, and IL-6.

Results: The cytotoxicity assay results suggested that the concentration for MK2 inhibitors less than 50.0 μM be non-toxic. The ELISA Kits also demonstrated that MK2 peptide inhibitor treatment significantly decreased the content of NO, TNF-, IL-1, and IL-6 in LPS-stimulated RAW264.7 cells. It was also demonstrated that a folate-targeted MK2 inhibitor was more effective than a non-targeted inhibitor.

Conclusion: This experiment demonstrates that LPS-induced macrophages can produce oxidative stress and inflammatory mediators. According to our research, pro-inflammatory mediators can be reduced by targeting folate receptor- positive (FR+) macrophages with an FR-linked anti-inflammatory MK2 peptide inhibitor in vitro, and the uptake was FR-specific.